International Journal of Medical Sciences

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25 May 2019

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Int J Med Sci 2018; 15(13):1508-1516. doi:10.7150/ijms.28106

Research Paper

Simvastatin Protects Heart from Pressure Overload Injury by Inhibiting Excessive Autophagy

Feifei Su1✉*, Miaoqian Shi2*, Jian Zhang3*, Qiangsun Zheng4, Dongwei Zhang1, Wei Zhang1, Haichang Wang1, Xue Li1

1. Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
2. Department of Cardiology, PLA Army General Hospital, No.5 Nanmen Cang, Dongcheng District, Beijing, 100700, China.
3. Department of Cardiology, Beijing Chest Hospital Heart Center, Capital Medical University, No.9. Beiguan Grand Street, Tongzhou District, Beijing, 101149, China.
4. Division of Cardiology, Second Affiliated Hospital of JiaoTong University, Xi'an, 710004, China.
* These authors contributed equally to this work.

Abstract

Cardiac hypertrophy is an independent predictor of cardiovascular morbidity and mortality. To identify the mechanisms by which simvastatin inhibits cardiac hypertrophy induced by pressure overload, we determined effects of simvastatin on 14-3-3 protein expression and autophagic activity. Simvastatin was administered intragastrically to Sprague-Dawley (SD) rats before abdominal aortic banding (AAB). Neonatal rat cardiomyocytes (NRCs) were treated with simvastatin before angiotensin II (AngII) stimulation. 14-3-3, LC3, and p62 protein levels were determined by western blot. Autophagy was also measured by the double-labeled red fluorescent protein-green fluorescent protein autophagy reporter system. Simvastatin alleviated excessive autophagy, characterized by a high LC3II/LC3I ratio and low level of p62, and blunted cardiac hypertrophy while increasing 14-3-3 protein expression in rats that had undergone AAB. In addition, it increased 14-3-3 expression and inhibited excessive autophagy in NRCs exposed to AngII. Our study demonstrated that simvastatin may inhibit excessive autophagy, increase 14-3-3 expression, and finally exert beneficial effects on cardioprotection against pressure overload.

Keywords: 14-3-3, autophagy, hydroxymethylglutaryl-CoA reductase inhibitors, simvastatin, hypertrophy

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Su F, Shi M, Zhang J, Zheng Q, Zhang D, Zhang W, Wang H, Li X. Simvastatin Protects Heart from Pressure Overload Injury by Inhibiting Excessive Autophagy. Int J Med Sci 2018; 15(13):1508-1516. doi:10.7150/ijms.28106. Available from http://www.medsci.org/v15p1508.htm